Aliases: Orctl1, Paht, Roat1
Gene name: Solute carrier organic anion transporter family 22 member 6
The classical organic anion transporter Oat1 was first cloned from the rat [1, 2], and this was followed by the identification of the human ortholog. rOat1, mainly expressed at the basolateral membrane of the renal proximal tubules, is responsible for the tubular uptake of organic anions from blood, such as p-aminohippurate (PAH), and also contributes to the excretion of salicylates and cephalosporins, among others [3-6]. rOat1 is also expressed at a lower level in the brain, preferentially in the cortex . Nucleoside analog antiviral drugs without a phosphate group are also transported by rOat1. Zidovudine, acyclovir, adefovir, cidofovir, zalcitabine, didanosine, lamivudine, stavudine, and trifluridine were shown to be substrates of rOat1, whereas foscarnet, a phosphate analog, was not. Weak inhibition was observed with acyclovir, amantadine, AZT, ganciclovir, and others . Anionic diuretics such as acetazolamide, bumetanide, furosemide, chlorothiazide, and hydrochlorothiazide were tested as possible substrates of rOat1. Low Ki values of furosemide and bumetanide indicated a high inhibitory potential of these drugs on rOat1 . Interaction of rOat1 with NSAIDs was demonstrated using an oocyte expression system. PAH uptake mediated by rOat1 was inhibited by diclofenac, ibuprofen, ketoprofen, naproxen, and piroxicam . Kynurenic acid, one of the final metabolites of tryptophan, is accepted as a uremic toxin , and increased kynurenic acid content in the brain has been linked to schizophrenia . Whereas kynurenic acid is a good substrate of human organic anion transporters hOAT1 and hOAT3 , the transport activity of rOat1 on kynurenic acid was comparatively low . Gaboxadol was also a substrate for the renal transporter rOat1 . Sulfonylureas and nateglinide interfere with rOat1, but these drugs themselves are not translocated by the transporter .
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4. Tojo, A., et al., Immunohistochemical localization of multispecific renal organic anion transporter 1 in rat kidney. J Am Soc Nephrol, 1999. 10(3): p. 464-71.
5. Uwai, Y., et al., Interaction and transport of thiazide diuretics, loop diuretics, and acetazolamide via rat renal organic anion transporter rOAT1. J Pharmacol Exp Ther, 2000. 295(1): p. 261-5.
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9. Vanholder, R., et al., Review on uremic toxins: classification, concentration, and interindividual variability. Kidney Int, 2003. 63(5): p. 1934-43.
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13. Larsen, M., et al., 5-Hydroxy-L-tryptophan alters gaboxadol pharmacokinetics in rats: involvement of PAT1 and rOat1 in gaboxadol absorption and elimination. Eur J Pharm Sci, 2010. 39(1-3): p. 68-75.
14. Uwai, Y., et al., Inhibitory effect of anti-diabetic agents on rat organic anion transporter rOAT1. Eur J Pharmacol, 2000. 398(2): p. 193-7.